TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13976	42151;42152;42153	chr2:178635263;178635262;178635261	chr2:179499990;179499989;179499988
N2AB	12335	37228;37229;37230	chr2:178635263;178635262;178635261	chr2:179499990;179499989;179499988
N2A	11408	34447;34448;34449	chr2:178635263;178635262;178635261	chr2:179499990;179499989;179499988
N2B	4911	14956;14957;14958	chr2:178635263;178635262;178635261	chr2:179499990;179499989;179499988
Novex-1	5036	15331;15332;15333	chr2:178635263;178635262;178635261	chr2:179499990;179499989;179499988
Novex-2	5103	15532;15533;15534	chr2:178635263;178635262;178635261	chr2:179499990;179499989;179499988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-90
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.0642
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/L	rs773772232	-0.849	0.041	N	0.382	0.048	0.201204373187	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/L	rs773772232	-0.849	0.041	N	0.382	0.048	0.201204373187	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85997E-06	0	0
I/N	None	None	0.911	N	0.821	0.311	0.610288044756	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.8248	likely_pathogenic	0.7902	pathogenic	-2.295	Highly Destabilizing	0.115	N	0.623	neutral	None	None	None	None	N
I/C	0.9557	likely_pathogenic	0.9242	pathogenic	-1.555	Destabilizing	0.944	D	0.725	deleterious	None	None	None	None	N
I/D	0.9963	likely_pathogenic	0.9939	pathogenic	-2.144	Highly Destabilizing	0.817	D	0.835	deleterious	None	None	None	None	N
I/E	0.9883	likely_pathogenic	0.982	pathogenic	-1.98	Destabilizing	0.817	D	0.789	deleterious	None	None	None	None	N
I/F	0.905	likely_pathogenic	0.8571	pathogenic	-1.347	Destabilizing	0.624	D	0.716	prob.delet.	N	0.437668413	None	None	N
I/G	0.9851	likely_pathogenic	0.9757	pathogenic	-2.785	Highly Destabilizing	0.817	D	0.747	deleterious	None	None	None	None	N
I/H	0.9927	likely_pathogenic	0.9869	pathogenic	-2.119	Highly Destabilizing	0.981	D	0.807	deleterious	None	None	None	None	N
I/K	0.9783	likely_pathogenic	0.9617	pathogenic	-1.626	Destabilizing	0.817	D	0.791	deleterious	None	None	None	None	N
I/L	0.4576	ambiguous	0.4225	ambiguous	-0.917	Destabilizing	0.041	N	0.382	neutral	N	0.409765984	None	None	N
I/M	0.609	likely_pathogenic	0.5107	ambiguous	-0.871	Destabilizing	0.624	D	0.713	prob.delet.	N	0.438880823	None	None	N
I/N	0.9653	likely_pathogenic	0.9467	pathogenic	-1.759	Destabilizing	0.911	D	0.821	deleterious	N	0.439092943	None	None	N
I/P	0.9951	likely_pathogenic	0.9917	pathogenic	-1.353	Destabilizing	0.931	D	0.833	deleterious	None	None	None	None	N
I/Q	0.9828	likely_pathogenic	0.9713	pathogenic	-1.72	Destabilizing	0.931	D	0.824	deleterious	None	None	None	None	N
I/R	0.9607	likely_pathogenic	0.9382	pathogenic	-1.267	Destabilizing	0.817	D	0.821	deleterious	None	None	None	None	N
I/S	0.9301	likely_pathogenic	0.8934	pathogenic	-2.492	Highly Destabilizing	0.624	D	0.74	deleterious	N	0.437668413	None	None	N
I/T	0.799	likely_pathogenic	0.7068	pathogenic	-2.192	Highly Destabilizing	0.321	N	0.675	prob.neutral	N	0.432695276	None	None	N
I/V	0.0936	likely_benign	0.0756	benign	-1.353	Destabilizing	None	N	0.125	neutral	N	0.304934168	None	None	N
I/W	0.998	likely_pathogenic	0.9958	pathogenic	-1.632	Destabilizing	0.981	D	0.785	deleterious	None	None	None	None	N
I/Y	0.9879	likely_pathogenic	0.979	pathogenic	-1.356	Destabilizing	0.817	D	0.781	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.